key: cord-266549-g8060w8v
authors: Gkentzi, Despoina; Karatza, Ageliki; Dimitriou, Gabriel
title: Challenges for the Pediatricians During the Coronavirus Disease 2019 Pandemic Start From the Neonatal Period
date: 2020-06-05
journal: Pediatr Infect Dis J
DOI: 10.1097/inf.0000000000002713
sha: 
doc_id: 266549
cord_uid: g8060w8v

nan

influenza-positive swab [22 (71%) with Influenza A, 9 (29%) with Influenza B]. Cough seems less prevalent in COVID-19 compared with other infected infants (Table 1) . While no deaths occurred in infants with COVID-19, 2 3 infants infected with CoV in Pneumostudy died, 2 of whom were co-infected with Streptococcus pneumoniae.

This report underscores the lack of major differences in the clinical features of severe acute respiratory syndrome coronavirus 2 and other types of CoV or influenza infections among infants despite limited clinical features reported. COVID-19 infection does not seem more severe than other CoV or influenza infections in this population, possibly as all infect Angiotensin-Converting Enzyme 2 receptors in the upper airways. As influenza, 5 the contribution of infants to the spread COVID-19 should be investigated. S. pneumoniae was codetected in the CoV-infected infants who died in Pneumo-study while bacterial co-detection was not reported by Wei et al. 2 Infants in both studies 2,3 were hospitalized limiting selection bias but small sample sizes weakened statistical power. The incidence of COVID-19 in infants less than 1-year-old is currently low, but studies are needed to describe the clinical features, prognosis and impact of infected infants on the COVID-19 spread.

*Pneumonia Study GABRIEL members: Gláucia Paranhos-Baccalà, Shally 

Milan. This is actually the current situation in various pediatric departments throughout Europe. We fully agree with the suggested management and approach, although the latter still poses major further logistical issues such as the availability of negative pressure rooms for all inpatients with suspected COVID-19 infection pending virologic confirmation. Moreover, 2 negative respiratory samples are required to rule out severe acute respiratory syndrome coronavirus 2 infection which means further inpatient stay and more resources needed. More data in the field are urgently required to guide the pediatricians further.

Apart though from the management of febrile children, pediatricians and the pediatric infectious diseases specialists will also have to face challenges with the infection during the neonatal period. Undoubtedly close monitoring of at-risk neonates is essential in the neonatal wards, but there are issues where evidence-based guidance is needed. The first priority is identifying the timing of infection (antenatally, perinatally or postnatally) and confirming its presence. Two recent reports from China suggest that in utero infection could be possible based on the measurement of IgM levels in neonates shortly after birth but no further confirmation of this with a positive reverse transcriptase-polymerase chain reaction test. 2,3 Therefore, although in utero transmission is possible, larger studies on infected women will bring further insight in the field. In the case of the in utero infected neonate, the timing of infection may have an impact on fetal development and possibly on long-term outcomes. We do not know as yet whether acquisition during first trimester of pregnancy is associated with birth defects and whether fetal infection is more likely in the advanced pregnancy stages following the patterns of other congenital infections. What we do know though is that antenatal infection with other coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome) is associated with possible miscarriage, intrauterine growth retardation prematurity and low birth weight. 4 Moreover, at present, we do not know how many molecular tests we need to perform and whether 2 tests are enough to rule out neonatal infection given that serology is not always reliable, as observed with other congenital infections. In addition to that, uncertainty exists as to whether respiratory specimens are enough or blood, stool or urine samples would offer more accurate results.

Last but not least separation of an infected mother from her offspring and feeding options are issues for further consideration. Some guidelines suggest complete separation of a COVID-19-positive mother and her baby for at least 14 days or until viral shedding clears, during which time direct breast-feeding is not recommended. 5 On the other hand, the Centre for Disease Control and Prevention and the Royal College of Obstetricians and Gynecologists recommend breast-feeding with strict contact precautions based on the fact that so far there is no evidence that the virus can be transferred via breast milk. For those women who are too sick to breast-feed, the recommendation is breast milk expression and avoidance of any contact with the baby.

In conclusion, the current pandemic poses several challenges to the pediatricians from the neonatal period throughout adolescence. Evidence-based recommendations 

Coronavirus infections in children including COVID-19

Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China

pneumonia GABRIEL network. Multicenter casecontrol study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network)

Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL) Network; Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL) Network. Microorganisms associated with pneumonia in children <5 years of age in developing and emerging countries: the GABRIEL pneumonia multicenter, prospective, case-control study

Influenza in children

SARS-CoV-2 infection in a pediatric department in Milan: a logistic rather than a clinical emergency

Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn

Antibodies in infants born to mothers with COVID-19 pneumonia

Coronavirus infections in children including COVID-19 an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children

Guidelines for pregnant women with suspected SARS-CoV-2 infection

The authors have no funding or conflicts of interest to disclose. N.K. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. N.K. contributed to the study concept and design; drafting of the article; Critical revision of the article for important intellectual content. originated in China and has rapidly spread worldwide. Currently, supportive therapy is the most effective treatment. Vaccination is one of the best options for the prevention of infectious diseases. However, a vaccine, as well as a specific proven treatment, remains elusive.The Bacillus Calmette-Guérin (BCG) vaccine is administered to more than one million children annually in countries with a high prevalence of tuberculosis. Recently, researchers hypothesized that it might also combat COVID-19 because of its broad ability to stimulate the immune system. 1 This is based on the fact that countries without universal policies of BCG vaccination (ie, Italy, the Netherlands, and the United States) have been more severely affected compared with countries with universal and long-standing BCG policies. 2 Therefore, some researchers are investigating the vaccine's effectiveness against COVID-19. 3 However, it should be emphasized that the causality is not yet proven; there is only one study predicting an association. 3 Generally, to clarify the causality between two variables, the Bradford Hill criteria is used. 4 To show the causality between the BCG vaccine and the severity of COVID-19, we have to confirm the following Bradford Hill criteria: specificity, temporality, reversibility, and experiment. Until the results of interventional studies are published, we cannot conclusively establish the utility of BCG against COVID-19.However, many people have misinterpreted this association as causation. This excessive expectation increases individual desire to be vaccinated with BCG. This will cause a big problem for Japanese infants, who, owing to the shortage of BCG, may not get the necessary vaccination. Producing adequate amounts of BCG to meet demands besides that for infant vaccination will take half a year because, at present, only the amount necessary for use in infants is manufactured. Apprehension regarding BCG shortage led the Japanese Society for Vaccinology to officially state that it does not recommend the use of BCG vaccine for the prevention of COVID-19. 5 However, under the current Japanese health care system, individuals willing to pay for individual vaccination cannot be prohibited from doing so. Therefore, emphasizing the lack of evidence and the cooperation of Japanese citizens is necessary. If infants in Japan do not receive BCG vaccines, tuberculosis might spread. We must prevent this from happening by publicizing inadequate evidence of causality between the BCG and prevention of the COVID-19. We also need to highlight the concern that a shortage of BCG would exacerbate the tuberculosis crisis among the infants in Japan.

Wayne State University Detroit, Michigan